Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE.

To the Editor, Since the beginning of the well-known severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, skin involvement both in adults and children has been signaled. 1,2 However, large-scale studies describing skin manifestations and their etiopathogenic correlation with coronavirus disease 2019 (COVID-19) in detail have not been reported yet. Through the analysis of emerging data from literature 3 and the direct observation of three patients with COVID-19 (SARS-CoV-2 detection from nasopharyngeal swab samples through RNA extraction) and dermatological manifestations, we have hypothesized different mechanisms for their development. CASE 1: A 55-year-old woman was admitted to the Infectious Diseases Department of the General Regional Hospital of Ancona for pyrexia, dry cough, and dyspnea. Upon admission, she had undergone nasopharyngeal swab for SARS-CoV-2 isolation, with positive laboratory report. The day before, she had performed a chest X-ray showing a right parahilar pulmonary consolidation. At the admission, high-resolution computed tomography scan of the chest revealed a diffuse bilateral ground-glass opacity, then diagnosis of COVID-19 interstitial pneumonia was made. Her comorbidities included obesity (BMI = 30.2) and hypertension, in treatment with Bisoprolol Fumarate 5 mg once a day. Dermatological consultation was immediately requested for skin rash appeared 72 hours before hospital admission. It was therefore observed a generalized urticarial skin rash characterized by erythematous, smooth, slightly elevated papules and wheals, associated to severe pruritus. The patient did not report neither similar episodes in the past, nor allergies to drugs or foods. Furthermore, the patient had not taken any new medication before the rash appeared. Blood test revealed normal blood count (no lymphopenia or lymphocytosis or eosinophilia), slight increase of procalcitonin serum level (0.14 ng/mL), C-reactive protein (CRP, 12.1 mg/dL), and liver enzymes (glutamic oxaloacetic transaminase [GOT], glutamate pyruvate transaminase [GPT], lactate dehydrogenase [LDH], gamma-glutamyl ranspeptidase [GGT] fourfold levels). A systemic treatment with intravenous daily administration of betamethasone sodium phosphate 4 mg and chlorphenamine maleate 10 mg, in addition to antiviral therapy with lopinavir/ritonavir for pneumonia, was started. In the LETTER TO THE EDITOR | 2333 A careful personal and family history should be collected for each patients, even if paucisymptomatic, in this subset of patients (with a careful epidemiological investigation of possible COVID-19 infection), claiming for SARS-CoV-2 nasofaryngeal swab.

focal hyperhidrosis, aesthetic medicine and neurological conditions with a strong efficacy and safety profile [1][2][3][4][5][6][7] . The enormous therapeutic potential of this drug contributed to a number of broad applications, especially in dermatological diseases. A large number of these indications are still lacking shared, approved protocols for dilution, doses, and timing of follow-up and retreatment. Also the injection techniques are still debated, depending on the operator's experience, angle of injection and depth. We have previously published a novel injection approach consisting in a needle adaptor that ensures a uniform administration of the toxin [3] . The aim of this review was to collect and analyze the published data concerning the most relevant off-label indications of BoNT-A. MethodsA PubMed search from 1950 to July 2016 was performed to identify any reports on the use of botulinum toxin in off-label indications concerning dermatology. We detected these articles using the terms "botulinum toxin dermatology," "botulinum toxin treatment," "botulinum toxin off-label," and meshed with a secondary search of studies pertaining to each indication. Only studies in English were reviewed. All studies that met the criteria were included and summarized in this review. KeywordsBotulinum toxin · Off-label therapy · Keloids · Hidradenitis suppurativa · Folds dermatitis Abstract Background: Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum which causes a flaccid muscle paralysis. It is currently used for aesthetic treatments and in the focal hyperhidrosis. Recently, botulinum toxin has also been used experimentally in many other dermatological conditions with good results. Objective: To review and analyze the possible botulinum toxin off-label applications published. Methods: A retrospective review of the published data was conducted. Conclusions: this potent drug can lead to several off-label indications of interest for dermatologists. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and dose protocols.

The clinical efficacy of ingenol mebutate on AKs is confirmed by its effect on angiogenesis, stem cell activity and cell proliferation in vivo.

Hidradenitis suppurativa is a chronic skin disease with an intense inflammatory activation. It typically affects the intertriginous areas with cysts, fistulae, and scarring extremely painful. Patients suffer from severe psychological impact. HS still results in a high unmet medical need with several underdiagnosed cases, probably due to the incomplete knowledge of the pathogenesis of HS. The use of botulinum toxin a has recently been proposed as an effective therapy for HS.